The war on drugs has a new front, and so far it appears to be a losing one.

Synthetic mimics of marijuana, dissociative drugs and stimulants - such as the "bath salts" allegedly consumed by Randy Eugene, the Florida man shot after a horrific face-eating assault - are growing in popularity and hard to control. Every time a compound is banned, overseas chemists synthesize a new version tweaked just enough to evade a law's letter.

It's a giant game of chemical Whack-a-Mole.

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"Manufacturers turn these things around so quickly. One week you'll have a product with compound X, the next week it's compound Y," said forensic toxicologist Kevin Shanks of AIT Laboratories, an Indiana-based chemical testing company.

"It's fascinating how fast it can occur, and it's fascinating to see the minute changes in chemical structure they'll come up with. It's similar, but it's different," Shanks continued.

During the last several years, the market for legal highs has exploded in North America and Europe. The names and ostensible purposes are almost comical - Cloud 9 Mad Hatter incense, Zombie Matter Ultra potpourri, Ivory Wave bath salts and Crystal Clean pipe cleaner - but the underlying chemistry is highly sophisticated.
Active ingredients in the drugs are compounds originally synthesized by institutional researchers whose esoteric scientific publications were mined by as-yet-unidentified chemists and neuroscientists working in Asia, where most of the new drugs appear to come from.

One class of popular cannabinoid mimics, for example, was developed by respected Clemson University organic chemist John Huffman, who sought to isolate marijuana's chemical properties for use in cancer research. Other "legal high" ingredients have similar pedigrees, with designers including researchers at Israel's Hebrew University and the pharmaceutical giant Pfizer.

While people raised on Reefer Madness-style exaggerations may be wary of claims that "legal high" drugs are dangerous, researchers say they're far more potent than the originals.

"The results are toxic and very dangerous, especially for vulnerable people - people with previous psychotic episodes - and the young," said Liana Fattore, a chemist at Italy's Institute of Neuroscience.

So far, however, these aren't working. In a May 14 Journal of Analytical Toxicology study, Shanks' team described AIT's tests of legal drugs purchased since the Drug Enforcement Agency's 2010 bans of three synthetic stimulants and five synthetic cannabinoids.

A full 95 percent of the products contained compounds not covered by the law. They'd been subtly tweaked so as to possess a different, legal molecular form while performing the same psychopharmaceutical role.

A Toxicology Letters study published earlier in May described similar adjustments in derivatives of pipradol, a controlled stimulant.

"If you want any evidence that drugs have won the drug war, you just need to read the scientific studies on legal highs," wrote Vaughan Bell at MindHacks, a neuroscience blog that's covered legal highs in depth.

While it's conceivable that laws could be adjusted to reflect each new ingredient, it would be highly impractical: Between 400 and 450 compounds were synthesized by Huffman alone, and those represent just one of four major groups of cannabinoid mimics.

Stimulant and dissociative derivatives are less numerous, the portfolio of possible derivatives still includes hundreds of forms. A compound-by-compound pursuit could last for decades.

An obvious alternative approach is to ban entire classes of similar compounds rather than focusing on individual forms. However, Shanks said this is easier said than done.

"The problem with that is, what does ‘chemically similar' really mean?" Shanks said. "Change the structure in a small way - move a molecule here, move something to the other side of the molecule - and while I might think it's an analogue, another chemist might disagree."

Shanks is a member of the Advisory Committee on Controlled Substance Analogues, an informal group of chemists, toxicologists and other experts trying to agree on common standards of chemical similarity.

"That's the crux of the entire problem," Shanks said. "The scientific community does not agree on what ‘analogue' essentially means."